These studies are targeted to define the biochemical whereby age-dependent changes in regulation of intermediary metabolism perturb physiological control systems, and thus, lead to a failure to maintain homeostasis in the aged. Topics include: 1) regulation of the carbohydrate and fat oxidation; 2) mechanism of control of pyruvate dehydrogenase activity by phosphorylation/dephosphorylation reactions; 3) loci of the defect in fatty acid oxidation in aged animals; 4) mechanism of ammoniagenesis and mitochondrial adaptation to acidosis; and 5) mechanism of regulation of the tricarboxylate cycle, the major energy-yielding pathway.